Nicotinate-adenine dinucleotide phosphate-induced Ca²⁺ release does not behave as a Ca²⁺-induced Ca²⁺-release system

We investigated the dependence of nicotinate-adenine dinucleotide phosphate (NAADP)-induced Ca^2t release from intracellular stores of sea urchin egg homogenates, upon extravesicular Ca²⁺. In contrast to the Ca²⁺ release induced by inositol 1′,4′,5′-trisphosphate (IP₃) or cyclic ADP-ribose (cADPR), the Ca²⁺ release induced by NAADP was completely independent of the free extravesicular Ca²⁺ over a wide range of concentrations (0-0.1 mM). The Ca²⁺ release triggered by either cADPR or IP₃ was biphasically modulated by extravesicular Ca²⁺, and the Ca²⁺ release by these agents was abolished when the extravesicular Ca²⁺ was removed by chelation with 2 mM EGTA. On the other hand, NAADP-triggered Ca²⁺ release was not influenced by EGTA. These data indicate that while both cADPR and IP₃ systems behave as functional Ca²⁺-induced Ca²⁺ release mechanisms, NAADP activates a Ca²⁺ release mechanism which is independent of the presence of extravesicular Ca²⁺. Therefore, the NAADP-sensitive Ca²⁺ release mechanisms may have a unique regulatory impact upon intracellular Ca²⁺ homoeostasis.